GPX2, also known as GSHPx-GI, is a selenoenzyme with glutathione peroxidase activity. Among the four Se-GPX isozymes (GPX1-4), it is closely related to GPX1 in terms of structure, substrate specificities, and subcellular localization. GPX2 expression is regulated by multiple pathways such as NRF2, WNT, p53, RARE, and it is mainly expressed in the digestive tract epithelium and more widely in epithelial tissues, concentrated in stem cell and proliferative compartments [1]. It is involved in maintaining hydroperoxide balance and may play a role in mucosal homeostasis, inflammation-related carcinogenesis, and other biological processes [1,2]. Genetic models, like gene knockout in mice, can be used to study its functions.

In gene knockout mouse studies, both Gpx1 and Gpx2 had to be knocked out to produce ileocolitis, indicating that GPX2 may have an interdependent relationship with GPX1 in maintaining proper peroxiredoxin function, although the exact role in relation to peroxiredoxin function is unclear [1]. In a mouse model of inflammation-associated colon carcinogenesis (AOM/DSS), GPX2 deletion increased inflammation and tumor development but decreased tumor size, demonstrating a Janus-faced role of GPX2 in inflammation-triggered carcinogenesis [2].

In conclusion, GPX2 is a key selenoenzyme involved in maintaining hydroperoxide balance and mucosal homeostasis. Studies using KO mouse models have revealed its complex role in inflammation-related carcinogenesis and intestinal inflammation, providing important insights into understanding the biological functions of GPX2 and its potential implications in related disease areas.